Cell lines are frequently used for manufacturing protein therapeutic products. Among all commonly used lines, Chinese hamster ovary (CHO) cells remained as the preferred mammalian cell line for the production of recombinant protein therapeutic. Currently, recombinant protein titers from CHO cell culture have reached the gram per liter range which is a 100-fold improvement over similar process in the 1980s. The significant improvement of titer can be attributed to progress in establishment of stable and high producing clones as well as optimization of culture process.
To improve protein production, various cell line engineering strategies have been employed focusing on extending the longevity of cell culture, accelerating the specific growth rate and increasing the maximum viable cell density. Also, cell line engineering has been employed to improve the folding, transport and secretion of the recombinant protein. Despite these efforts, however, further improvement is needed for the overall efficiency of protein production.